Colorectal cancer is the second most common cancer in the United Kingdom and other developed countries in the West. Although usually not familial there is a rare dominantly inherited susceptibility to colon cancer, Familial Adenomatous Polyposis (FAP or Familial Polyposis Coli). During adolescence affected individuals develop from a few hundred to over a thousand adenomatous polyps in their large bowel. These have a sufficiently high probability of giving rise to adenocarcinomas that prophylactic removal of the colon is recommended in diagnosed FAP individuals. Polyps may also occur elsewhere in the gastrointestinal tract and the condition is often associated with other extracolonic lesions, such as epidermoid cysts, jaw osteomata and fibrous desmoid tumours. .sup.1,2,3,4
Adenomata have been suggested to be precancerous states for the majority of colorectal tumours .sup.5,6. Knudson.sup.7 has suggested that in both familial and non-familial cancers, dominant genes give rise to cancer susceptibility. He further proposed that these mutations act recessively at the cellular level, and that both copies of the gene must be lost for the cancer to develop. In sporadic cases both events occur somatically while in dominant familial cases susceptibility is inherited through a germ line mutation and the cancer develops following a somatic change in the homologous allele. This model was first substantiated by the elegant molecular work on retinoblastoma .sup.2a. Following the linkage of the disorder to chromosome 13.sup.3a, Cavenee et al.sup.2a, using polymorphic DNA markers for this chromosome, showed loss of heterozygosity in tumour material compared to normal tissue from the same patient, in both familial and non-familial forms. Similar results have now been obtained, following cytogenetic evidence which suggested the localisation of the disease on a specific chromosome, for Wilm's tumours .sup.4a-7a, acoustic neuromas.sup.8a as well as several other tumours .sup.9a,10a.